Results of many studies have shown that following brain injury, there occurs an increase in the permeability of the cerebral microvasculature. The morphological expression of this increase in permeability in the blood-brain barrier (BBB) is the formation of pinocytic vesicles and tubular channels. The former structures are known as the pinocytic vesicular transport system (PTS) and the latter is defined by us asthe canalicular transport system (CTS). Although this CTS has been observed in various animal species in several experimental models of brian injury, the exact mechanism of the formation of the CTS and its relationship to the PTS remains unclear. The goal of the present proposal therefore, is to study: (1) relationships between the PTS and CTS in normal an phtologically altered BBB. This will be accomplished using ultrastructural techniques including studies of high resolution tilt electron microscopy and enzyme cytochemistry employing several phosphatase enzymes (alkaline phosphatase and nucleoside diphosphatase), known to change in their localization following BBB damage, (2) BBB permeability will be tested using the protein tracer horseradish peroxidase (HRP), (3) relationships between he CTS and lysosomes of the damaged endothelial cells will be studied using acid phosphatase, as an enzymatic marker of lysosomes, (4) the effects of several types of fixatives on the fine structure morphology of the PTS and CTS will also be examined. Data from BBB studies will be compared to microvascular transport of normal skeletal muscle employing HRP, tilt electron microscopy and enzyme cytochemistry. To accomplish our goals, two models of increased BBB permeability in the mouse will be used including mechanical brain trauma and infection by a scrapie agent.